Pattern of Residual Submucosal Involvement after Neoadjuvant Therapy for Rectal Cancer: A Rationale for the Utility of Endoscopic Submucosal Resection.

Background and Objectives: Full-thickness trans anal local excision for tumors with favorable response following neoadjuvant therapy for locally advanced rectal cancer (LARC) is a common strategy for organ preservation, but it could be associated with a high rate of postoperative complications. We describe the incidence and pattern of submucosal involvement in surgical specimens following neoadjuvant therapy for LARC and whether limiting local excision of the residual tumor bed to only mucosal/submucosal layers of the rectal wall is sufficient for accurately predicting the ypT status of residual cancer, providing a pathological rationale to replace full-thickness local excision by endoscopic submucosal resection. Materials and Methods: This was a single-institution retrospective study conducted at a teaching community hospital. We reviewed clinical and pathological findings with slides of 82 patients diagnosed with LARC treated at our center between 2006 and 2020. Eligibility criteria mirrored our current organ preservation trials. Results: No tumor was found in surgical specimens in 28 cases (34%). Additionally, 4, 22, 27, and 1 cases were staged as ypT1, ypT2, ypT3, and ypT4, respectively. Residual malignant cells were found in the submucosal layer in 98% of cases with ypT+ stage, with 'skip lesions' in only 2% of cases. Conclusions: A very high incidence of submucosal involvement is noticed in residual tumors after neoadjuvant therapy, providing pathological rationale to study the role of endoscopic submucosal resection as a restaging tool for tumors with favorable response after neoadjuvant therapy when organ preservation strategy is pursued. This study was limited by its retrospective design and relatively small number of patients.

Factors predicting nodal metastasis in endometrial cancer.

PURPOSE: Evaluation of lymph node (LN) metastases in endometrial carcinoma (EC) is an important prognostic factor and a required element of cancer staging. The purpose of this study is to analyze what factors might predict the likelihood of nodal involvement in EC. METHODS: A retrospective search of our institutional database for hysterectomies with associated LN dissection in women with EC revealed 207 cases between 2005 and 2012. Cases with primary EC, irrespective of histologic subtype, including carcinosarcomas were included in the study, but pure sarcomas were excluded. We evaluated various factors including tumor size (TS; ≤2.0 cm and >2.0 cm), depth of myometrial invasion (DMI; absent, ≤50 %, >50 %), positive pelvic cytology (PPC), cervical stromal invasion (CSI), and lymph-vascular invasion (LVI), to determine which factors correlated with the presence of LN metastasis. RESULTS: Of the 207 (age = 62.29 ± 10.9, mean ± SD) cases of EC with LN dissection in our study group, 34 (16.42 %) had positive LNs. On univariate analysis, we found that TS (p = 0.04), tumor grade (Grade I and II versus grade III, p < 0.0001), DMI (p < 0.0001), CSI (p < 0.0001), LVI (p < 0.0001), and PPC (p = 0.001) showed statistically significant correlation with LN metastasis. However, on multivariate analysis, only DMI (p = 0.002) and LVI (p = 0.004) independently showed statistically significant correlation with LN metastasis. In addition, 18 (8.7 %) grade I and II (well/moderately differentiated) tumors with TS ≤2.0 cm and <50 % DMI showed no LN metastasis, LVI, CSI, or PPC. CONCLUSION: We concluded that DMI and LVI were independent factors predictive of LN metastasis.

Cytohistologic correlation in premenopausal and postmenopausal women.

OBJECTIVE: This study was conducted to compare the correlation between Pap smear and colposcopic biopsy findings in premenopausal and postmenopausal women. STUDY DESIGN: A total of 68,738 ThinPrep Pap smears were done in 2011 in our institution, and of these, 865 of the women (787 premenopausal and 78 postmenopausal) had subsequent colposcopic directed biopsies performed within 3 months of obtaining the results. RESULTS: We discovered that 52.5% of the Pap smears in postmenopausal women versus 33.6% in premenopausal women were classified as false positive (FP), with respect to the biopsy, and of these, 47.6 vs. 17% cases had no transformation zone (TZ) on the subsequent biopsies, respectively. Interestingly, with respect to high-risk human papilloma virus (hrHPV) testing in patients having both Pap smear and biopsies performed, we found the Pap smear diagnoses were a better predictor of positive hrHPV than the respective colposcopic biopsies. CONCLUSION: As many of the FP postmenopausal women had an absent TZ (47.6%) on biopsy, and because the majority (83.3%) of those which had hrHPV testing were positive, we suggest that this indicates a potential sampling error on biopsy, perhaps due to an inability to visualize the involved area in older women due to an upward migration of the TZ.

Prognostic Utility of Tumor-Infiltrating Lymphocytes in Noncolorectal Gastrointestinal Malignancies.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and mismatch repair gene mutation (MMR) status are emerging biomarkers in immunotherapy. MMR status and TILs have significant clinical implications with regard to treatment with checkpoint inhibitors. We designed a study to determine the frequency and prognostic utility of TILs and MMR in advanced unresectable noncolorectal gastrointestinal (NCGI) malignancies. METHODS: This is a retrospective cohort study of patients who were diagnosed with advanced noncolorectal gastrointestinal tumors. Biopsy specimens were tested for MMR status by immunohistochemistry along with evaluation of TILs. Kaplan-Meier analysis was performed to determine the impact of TILS and MMR on survival. RESULTS: We analyzed 146 patients; the mean age at diagnosis was 66.4 ± 11.2 years. 65.8% patients were male, and 62.3% patients had stage 4 disease. All cases had proficient MMR status. The percentage of patients with TILs >5 was 50.7%. There was no statistically significant difference in median overall survival (OS) by TILs when stratified by stage of tumor. When stratified by type of tumor, median OS by TILs level was significantly different for hepatocellular cancers (⩽5 TILs, 86 days versus >5 TILs 312 days, P = .031). CONCLUSIONS: Our study suggests that MMR-deficient tumors are quite rare in advanced NCGI malignancies. More than 5 TILs per high power field, evaluated simply on a routine hematoxylin and eosin-stained glass slide confer a better prognosis to most noncolorectal gastrointestinal malignancies, especially hepatocellular carcinoma. This has immense clinical utility with regard to eligibility for immunotherapy.

Role of "Second Look" Lymph Node Search in Harvesting Optimal Number of Lymph Nodes for Staging of Colorectal Carcinoma.

As with other malignancies, lymph node metastasis is an important staging element and prognostic factor in colorectal carcinomas. The number of involved lymph nodes is directly related to decreased 5-year overall survival for all pT stages according to United States Surveillance, Epidemiology, and End Results (SEER) cancer registry database. The National Quality Forum specifies that the presence of at least 12 lymph nodes in a surgical resection is one of the key quality measures for the evaluation of colorectal cancer. Therefore, the harvesting of a minimum of twelve lymph nodes is the most widely accepted standard for evaluating colorectal cancer. Since this is an accepted quality standard, a second attempt at lymph node dissection in the gross specimen is often performed when the initial lymph node count is less than 12, incurring a delay in reporting and additional expense. However, this is an arbitrary number and not based on any hard scientific evidence. We decided to investigate whether the additional effort and expense of submitting additional lymph nodes had any effect on pathologic lymph node staging (pN). We identified a total of 99 colectomies for colorectal cancer in which the prosector subsequently submitted additional lymph nodes following initial review. The mean lymph node count increased from 8.3 ± 7.5 on initial search to 14.6 ± 8.0 following submission of additional sections. The number of cases meeting the target of 12 lymph nodes increased from 14 to 69. Examination of the additional lymph nodes resulted in pathologic upstaging (pN) of five cases. Gross reexamination and submission of additional lymph nodes may provide more accurate staging in a limited number of cases. Whether exhaustive submission of mesenteric fat or fat-clearing methods is justified will need to be further investigated.

Reporting endometrial cells in Papanicolaou smears of women age 40 and older: a qualifying educational note could prevent unnecessary follow-up biopsy.

OBJECTIVE: To determine the impact of adding a qualifying educational note when exfoliated endometrial cells were present in the first half of the menstrual cycle. STUDY DESIGN: We identified all Pap smears that had endometrial cells in women > or = 40 years, between July and November, 2004. When endometrial cells were seen in the first half of menstrual cycle, it was stated that, "endometrial cells correlate with the menstrual history provided." We then attempted to determine if this qualifying comment had an impact on the decision to obtain a follow-up endometrial biopsy. RESULTS: A total of 325 women were identified. Of these, 51 (15.7%) had follow-up endometrial biopsy without clinical evidence of endometrial pathology, compared to a rate of 36.9% before implementation of the note (p < 0.0001). Biopsies were performed in 21 of 195 (10.8%) when the note indicated that endometrial cells correlated with menstrual history, compared to 30 of 130 (23%) in whom a different note was appended because endometrial cells were out of phase or patients were postmenopausal (p = 0.0032). Biopsies did not reveal significant endometrial pathology in any of the 51 patients. CONCLUSION: Adding an educational note when endometrial cells are reported in the first half of the menstrual cycle in women > or = 40 years may help reduce unnecessary biopsies.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells reported in an asymptomatic patient: a rare case and literature review.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare and poorly described pancreatic malignancy. It is comprised of mononuclear, pleomorphic, and undifferentiated cells as well as osteoclast-like giant cells (OGC's). It constitutes less than 1% of pancreatic non-endocrine neoplasia and is twice as likely to occur in females as in males. Its histopathologic properties remain poorly understood. It is suspected that UC-OGC is of epithelial origin that can then transition to mesenchymal elements. As part of this study, we describe a case of a malignant pancreatic neoplasm that was discovered in a 69-year old patient as an incidental finding. We also provide an overview of previously published data to highlight UC-OGC's clinical and pathologic features.

Cytologic features of urothelial carcinoma in catheterized urine with cellular fragments.

OBJECTIVE: To identify architectural and cytomorphologic differences that might help distinguish urothelial neoplasms from instrumentation artifact. STUDY DESIGN: We examined 73 cytologic smears of catheterized urine containing urothelial cell clusters between 1998 and 2004. All patients had at least 1 follow-up biopsy. Smears were reviewed for several morphologic features blindly, without knowledge of the follow-up diagnosis. RESULTS: Of the 73 smears, 39 had a benign diagnosis on follow-up biopsy, and 34 had urothelial carcinoma. Cytoplasmic collar, regular and rounded fragment borders, and fine nuclear chromatin were statistically more common in benign smears than those with urothelial carcinoma (p < 0.0001). No significant differences were identified with regard to the presence of background inflammation or nucleoli in the urine specimens. Of the 17 smears that had a cytoplasmic collar, regular fragment borders and fine nuclear chromatin, only 1 (6%) was found to have urothelial carcinoma on follow-up biopsy. All 20 smears in which all 3 features were absent were proven malignant on biopsy. CONCLUSION: Certain architectural and nuclear features can help differentiate urothelial neoplasms from instrumentation artifact in urine cytologic smears.

Gastric schwannoma: a rare but important differential diagnosis of a gastric submucosal mass.

Schwannomas are generally slow growing asymptomatic neoplasms that rarely occur in the GI tract. However, if found, the most common site is the stomach. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, and 60-70% of them occur in the stomach. Owing to their typical presentation as submucosal neoplasms, gastric schwannomas and GISTs appear grossly similar. Accordingly, the differential diagnosis for a gastric submucosal mass should include gastric schwannomas. Furthermore, GI schwannomas are benign neoplasms with excellent prognosis after surgical resection, whereas 10-30% of GISTs have malignant behavior. Hence, it is important to distinguish gastric schwannomas from GISTs to make an accurate diagnosis to optimally guide treatment options. Nevertheless, owing to the paucity of gastric schwannomas, the index of suspicion for this diagnosis is low. We report a rare case of gastric schwannoma in 53-year-old woman who underwent laparoscopic partial gastrectomy under the suspicion of a GIST preoperatively but confirmed to have a gastric schwannoma postoperatively. This case underscores the importance of including gastric schwannomas in the differential diagnosis when preoperative imaging studies reveal a submucosal, exophytic gastric mass. For a gastric schwannoma, complete margin negative surgical resection is the curative treatment of choice.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells reported in an asymptomatic patient: a rare case and literature review

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare and poorly described pancreatic malignancy. It is comprised of mononuclear, pleomorphic, and undifferentiated cells as well as osteoclast-like giant cells (OGC's). It constitutes less than 1% of pancreatic non-endocrine neoplasia and is twice as likely to occur in females as in males. Its histopathologic properties remain poorly understood. It is suspected that UC-OGC is of epithelial origin that can then transition to mesenchymal elements. As part of this study, we describe a case of a malignant pancreatic neoplasm that was discovered in a 69-year old patient as an incidental finding. We also provide an overview of previously published data to highlight UC-OGC's clinical and pathologic features.

Sarcomatoid carcinoma of esophagus.

Sarcomatoid carcinoma of the esophagus is an uncommon malignancy, representing approximately 2% of esophageal carcinomas. It has also been referred to as carcinosarcoma, pseudosarcoma, pseudosarcomatous squamous cell carcinoma, spindle cell carcinoma, and polypoid carcinoma, reflecting the uncertainty of its pathogenesis. Histologically, carcinomatous and sarcomatous components coexist. The clinical and radiologic findings resemble other esophageal neoplasms. Sarcomatoid carcinoma often presents as a large, intraluminal, polypoid mass on barium esophagram. Despite its size, however, sarcomatoid carcinoma has a more favorable prognosis than other malignant esophageal neoplasms, likely because of its exophytic growth into the lumen, rather than deep invasion. This article provides a brief overview of the clinicopathologic features and possible pathogenesis of this uncommon tumor.

Nearly identical near-haploid karyotype in a peritoneal mesothelioma and a retroperitoneal malignant peripheral nerve sheath tumor.

The presence of a near-haploid karyotype is a rare finding in human malignancies, most frequently occurring in acute leukemia. In solid tumors, a near-haploid karyotype has been reported in fewer than 40 cases. We report two nearly identical near-haploid karyotypes from two distinctly different tumor types. The first case is a biphasic malignant mesothelioma from a 53-year-old white woman forming a large retroperitoneal mass. Cytogenetic evaluation revealed a primary hyperdiploid cell population as well as near-haploid and hypertetraploid populations with an overall karyotype of 27,XX,i(5)(p10),+7,add(15)(p11.2),+dic(1;20)(p13;p13)[2]/54,idemx2[90]/101-108,idemx4[19]. The second case is a large pelvic mass from a 48-year-old man. Histologic examination identified a malignant peripheral nerve sheath tumor displaying a karyotype of 26,X,+i(5)(p10),+7,der(15)t(1;15)(q12;p12),+20[5]/52,idemx2[20]. Herein we discuss the potential relationship between these two disparate neoplasms with nearly identical near-haploid karyotypes and present a literature review.

High-grade pancreatic intraepithelial neoplasia in a patient with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is caused by mutation of the adenomatous polyposis coli (APC) gene and is characterized by multiple colorectal adenomas and tumors of other organs and sites. A 58-year-old woman with FAP syndrome and previous total colectomy presented for routine follow-up examination. Abdominal ultrasound and subsequent endoscopic evaluation revealed ampullary and duodenal polyps, as well as inhomogeneity of the pancreatic head. A pancreaticoduodenectomy confirmed multiple duodenal adenomas. In addition, high-grade pancreatic intraepithelial neoplasia (PanIN-3) was found in the smaller pancreatic ducts. Pancreatic precancerous lesions have only rarely been described in FAP, including 2 pancreatic duct adenomas and 2 intraductal papillary mucinous neoplasms. A review of the world English literature revealed no reports of PanIN-3 in association with FAP. Further studies are required to determine if patients with FAP are at increased risk for pancreatic premalignant lesions.